January-February 2020

IN FOCUS

What your patient is taking and its effect on the eyeAlpha-1 blockers, the iris, and ophthalmic surgery

by Chiles Samaniego Contributing Writer

This is a patient on tamsulosin referred after complicated cataract surgery due to IFIS. There is iris damage and
anterior and posterior capsule damage with dislocation of the IOL.
Source: Steven Safran, MD

The IOL has dislocated into the back of the eye and is sitting on the retina. One haptic appears to be kinked.
Source: Steven Safran, MD

Same patient as in the prior two photos at 1 week after pars plana vitrectomy, exchange of damaged IOL for sutured PCIOL, and iris repair.
Source: Steven Safran, MD

Cataract surgeons are seeing more patients who have used—or are sing—tamsulosin.
“Tamsulosin is one of the most frequently used urologic agents in males for reduced urinary flow,” William Myers, MD, told EyeWorld. “As many patients undergoing cataract surgery have concomitant prostatic hypertrophy, many are already on or have tried tamsulosin. At the VA, nearly 75% patients are not naive with respect to alpha blockers.”
“A significant percentage of patients are taking these medications, most commonly for benign prostate hyperplasia,” Bryan Lee, MD, JD, agreed. “However, they are used for other reasons, such as making it easier to remove a Foley catheter or to help pass a kidney stone. They are also being used more commonly in women, so it is important to ask for a history of use and to cover not only tamsulosin but also the other medications with the same mechanism of action.”
EyeWorld corresponded with Drs. Lee, Myers, and Steven Safran, MD, to discuss the effects of alpha-1 adrenergic antagonists (or blockers) on the eye and find out what ophthalmologists need to know about their use.

Iris changes

Intraoperative floppy iris syndrome (IFIS) is the main concern when it comes to patients with a history of alpha-1 blocker use. “IFIS was first reported as an association by Campbell and Chang in 2005,”1 Dr. Myers said. “This creates increased risk of iris instability and pupil constriction during cataract surgery, increasing the risk of complications. Most patients are male, but tamsulosin is also used in female patients with urinary flow issues.”
In his experience, alpha-1 blockers can affect the iris after just one dose. “I cared for a patient with IFIS who had to stop tamsulosin after a single dose as he had a neuroleptic seizure develop,” he said.
Dr. Safran offered a different experience. “Some patients are on these medications for years with little effect and others within a few months can see an effect,” he said. However, he emphasized that “[t]he effect once it kicks in is permanent because there are histologic changes to the iris with atrophy of the dilator muscles.”
These changes were detailed by Ricardo Santaella, MD, and colleagues in a paper published in Ophthalmology.2 The retrospective, case-control study involved 51 cadaveric eyes from 27 patients—14 of whom used tamsulosin, leaving 13 in the control group. Dr. Santaella and his colleagues reviewed patient histories, recorded duration and dosage of tamsulosin use, and conducted light microscopic review and morphometric analysis of the eyes, measuring the maximum and minimum iris dilator muscle thickness and iris stromal thickness.
The group found that the “mean iris dilator muscle thickness in the tamsulosin-treated group (6.53±1.99 µm) was significantly thinner compared with that of the control group (8.50±1.61 µm)(p=0.006),” though no direct relationship was found between the iris changes and the dose and duration of tamsulosin use.
Because the effect is irreversible, the doctors agreed that there is no point asking the patient to stop using the blocker prior to surgery.
“I never ask patients to stop, I just want to make sure that I know about a history of current or prior use,” Dr. Lee said.
“The only reason to stop the medication is if they just started it,” Dr. Safran said. “If they have been on it for a while and the effect is already in place on the iris, then stopping it will make no difference.”

Medical intervention

So what can be done to reduce a floppy iris?
“There are a few different approaches to try to reduce it medically,” Dr. Lee said. “I usually use epinephrine in the bottle and inject phenylephrine into the anterior chamber to try to improve stability of the iris if I am concerned. You can use a dispersive viscoelastic to try to hold the iris in position early in the case, but eventually that OVD is going to have to be removed.” Dr. Lee said he does not use the brand name phenylephrine and ketorolac (Omidria, Omeros), using instead intracameral phenylephrine at his surgery center.
“I find that use of a concentration of epinephrine in the anterior chamber at the beginning of surgery can be very helpful to prevent IFIS in patients on alpha blockers,” Dr. Safran said. “Others use intraoperative phenylephrine either compounded or in the commercial product Omidria.” Dr. Safran said that he prefers the use of strong epi (1 ampule mixed with 4 cc balanced salt solution).
Going into further detail, Dr. Myers said: “Prophylactic intraocular adrenergic agents, such as epinephrine buffered to neutral pH as in epi-Shugarcaine, will ameliorate the symptoms. Those surgeons who routinely dilated patients with intracameral adrenergic agents and lidocaine did not see IFIS at all. Rarely, reduction of pupil size that was gradual and controlled occurred but no iris billowing or rapid miosis. This is a case of having a cure for a disease before the disease existed. Atropine has been suggested as well, but it risks inducing urinary blockage. Topical agents are ineffective.”
Omidria was FDA approved in May 2014 as a phenylephrine 1% and ketorolac 0.3% intraocular solution for intraoperative miosis prevention and postop pain management. It currently has extended pass-through status, and in 2019 CMS established a permanent J code.

Intraop management

Medical intervention can be enough to deal with IFIS. “Pharmacologic management of IFIS has been satisfactory without typically resorting to more expensive devices,” Dr. Myers said.
However, “[i]f the pupil size is inadequate to complete a capsulorhexis after the intracameral dilation agents and OVD are instilled, then I proceed to using either hooks or less commonly rings,” he added. “The decision is based on the pupil size and not the potential for IFIS developing. It is better to place hooks or rings prior to capsulorhexis to avoid damage to the capsule.”
“Iris retractors are my choice for patients where the pupil dilates poorly and the patient is on alpha blockers,” Dr. Safran said. “They are safe and work extremely well.”
Surgeons should use iris dilating devices with caution. “Any time you are using a device to manipulate the iris, there is a risk of causing an irregular pupil, iridodialysis, or bleeding,” Dr. Lee said. “However, these are rare problems, and most cataract surgeons are very familiar with using mechanical dilation.”
Although other devices such as the Malyugin ring work well, Dr. Lee prefers reusable hooks because they allow the surgeon to stretch the iris out more to get it out of the way, which IFIS irises tolerate well. Hooks can be left in later to verify toric IOL position at the end of the case and take up less space in a shallow chamber. Nevertheless, he will prefer a ring in certain cases, such as small lid fissures, uncooperative patients, or keratoconus.

Usual and unusual suspects

Among the alpha-1 adrenergic antagonists, “tamsulosin and silodosin are the two most likely to cause significant IFIS,” probably due to their being selective alpha blockers, Dr. Lee said. “It’s important to remember that tamsulosin is also in a combination with dutasteride called Jalyn and that women are now taking tamsulosin more frequently.”
However, it’s just as important to remember that alpha blockers aren’t the only possible causes of IFIS. “Tamsulosin is the agent most associated with IFIS, but other causes are anything that might affect the iris dilator muscle, including other alpha blockers, diabetes, and certain viral infections,” Dr. Myers said. “For this reason, I use intracameral dilation with phenylephrine and lidocaine on every patient, regardless of their use of alpha blockers systemically.” Dr. Safran also added that over-the-counter saw palmetto has been shown to cause IFIS. This is important to ask for in men (and some women) who might be using it and not mention it.

At a glance

• While most frequently used in men to manage prostatic hypertrophy, alpha-1 adrenergic blockers are also used to ease the removal of a catheter and help pass a kidney stone. They are also being used by women.
• Alpha-1 blockers effect irreversible histologic changes in the iris, with no direct relationship to dose or duration of use.
• Pharmacological management with epinephrine and phenylephrine can be enough to manage a floppy iris, but iris hooks and rings can also be useful.
• Ophthalmologists should be aware of other possible causes of IFIS, including diabetes and some viral infections.